Liver slices prepared at 16 hr post-hepatectomy and incubated in vitro will progress through a wave of DNA synthesis (S-phase) similar to that seen in vivo. However, slices prepared at 14 hr post-hepatectomy will not initiate DNA synthesis. The addition of calf serum or fetal calf serum to the incubation media does not affect these results. These preliminary studies are interpreted as indicating that between 14 and 16 hr after partial hepatectomy there exists a critical period during which exposure to a systemic factor(s) commits hepatic cells to enter a round of DNA synthesis. The goal of this proposed research project is to develop and refine this in vitro system to study the regulation of mammalian cell division. Normal rats, and those fed the hepatic carcinogens 3'-methyl-4-dimethylaminoazobenzene or 2-acetylaminofluorene will be used for these experiments. Liver slices prepared at 14 hr post-hepatectomy will be used to study factors affecting the G1 to S-phase conversion, and those prepared at 16 hr after the operation will be used to study progression through the S-phase. DNA synthesis will be monitored by measuring the incorporation of radioactive precursors and by autoradiography. Regenerating liver is the model system to be employed in these studies, because it provides a means to study a normal mammalian cell population in which cells progress through the cell cycle in a synchronous manner and growth stops after one or two rounds of cell division. This proposed research project may aid in discerning control points for the regulation of the cell cycle and in elucidating those actions of chemical carcinogens that result in aberrant control.